The PRINCE-BC trial: precision regional irradiation of nodal stations for clinical evaluation of high-risk pN0 breast cancer – a phase III, open-label, randomized controlled trial

Breast cancer is the most prevalent malignancy among women, posing a significant threat to female health. Radiation therapy serves as a critical component of comprehensive breast cancer treatment, yet its clinical benefit varies substantially across patients with differing recurrence risks. In the era of precision radiation therapy, optimizing the "escalation" or "de-escalation" of radiation therapy regimens based on individualized recurrence risk assessment to maximize net therapeutic benefit for early-stage breast cancer patients has emerged as a key research focus. Previous precision radiation therapy studies for postoperative early-stage pN0 breast cancer primarily centered on treatment de-escalation for low-risk cohorts, while clinical investigations on radiation therapy escalation for high-risk pN0 patients remain scarce. This was a prospective, open-labelled, randomized controlled trial aimed to investigate whether the addition of regional node irradiation (RNI) to whole breast irradiation (WBI)/chest wall irradiation (CWI) could improve disease-free survival in clinical high-risk pN0 breast cancer in comparison to WBI/CWI alone. Clinical high-risk was defined as breast cancer patients presented with two or more high-risk factors [tumor size (>2cm), tumor site (medial and central quadrants), ki-67 level (>14%), and Lympho-vascular Invasion Positive (LVI+)]. A total of 1355 participants would be recruited and randomized in a 1:1 ratio into RNI group and non-RNI group. All patients would receive standardized postoperative irradiation dose for WBI/CWI with or without RNI, both hypo-fractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions were allowed. For patient treated with breast-conserving surgery, sequential tumor bed boost irradiation could be delivered at the treating physician's discretion, based on individual risk factors such as close margins, high grade, or young age. (conventional regimen 10Gy/5Fx; hypo-fraction regimen: 10.68 Gy/4 Fx or 10Gy/4Fx) This is the first large randomized controlled trial to precisely guide decisions regarding regional nodal irradiation (RNI) for clinically high-risk pN0 breast cancer patients. In the era of precision and individualized radiotherapy, our research would provide high level evidence-based recommendations for patients with early-stage high-risk pN0 breast cancer. ClinicalTrials.gov Identifier NCT05976412 (https://clinicaltrials.gov/search?term=NCT05976412). Date of registration: July 28, 2023. Status: Recruiting.